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SARS-CoV-2 Antibody Discovery Strategy 

2020.03.24

 

NovoBind is an animal health company developing antibody fragments derived from the VHH domain of llama heavy chain only antibodies (nanobodies*) for animal feed applications. With the emergence of COVID-19, caused by SARS-CoV-2 (also known as 2019-nCoV), we quickly realized that these nanobodies could be applied to SARS-CoV-2 as well.

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NovoBind hypothesizes that the best-known site for a nanobody to neutralize of SARS-CoV-2 is at the surface of the ACE2-receptor binding domain (RBD) of the Spike protein (also known as S Protein). Nanobodies have previously been raised against the RBD of MERS-CoV [1,2]. These antibodies could protect mice prophylactically before MERS-CoV exposure [2] or could prevent the death of mice if applied therapeutically up to three days after exposure to MERS-CoV [1].

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Thanks to the generosity of our Coalition, NovoBind has the SARS-CoV-2 Spike RBD in hand and will screen existing nanobody libraries for binders. Simultaneously, two llamas will be immunized with the Spike RBD. NovoBind anticipates beginning to identify SARS-CoV-2 Spike RBD-binding nanobodies from the immunized llamas in late April 2020.

 

It has recently been demonstrated that monoclonal antibodies that bind SARS-CoV Spike RBD fail to bind SARS-CoV-2 Spike RBD, likely due to the significant amino acid sequence diversity between the two RBDs [3]. During the antibody discovery phase of this project, NovoBind aims to shortlist nanobodies that bind SARS-CoV-2 Spike RBD but fail to bind SARS-CoV Spike RBD as these have a higher likelihood of neutralizing SARS-CoV-2 than those nanobodies that bind both RBDs.

 

NovoBind intends to use an open source biology model to share the following results:

  1. Spike RBD protein constructs expressed and protein quality control data.

  2. Llama immunization schedule and ELISAs to demonstrate the development of Spike RBD-specific immune responses.

  3. Phage ELISA data from Spike RBD-binding nanobodies.

  4. Protein and DNA sequences of unique nanobodies identified by Phage ELISA.

 

References

1.           Zhao, G. et al. A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV. J. Virol. 92, e00837-18 (2018).

2.           Stalin Raj, V. et al. Chimeric camel/human heavy-chain antibodies protect against MERS-CoV infection. Sci. Adv. 4, eaas9667–eaas9667 (2018).

3.           Wrapp, D. et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science (80-. ). eabb2507 (2020) doi:10.1126/science.abb2507.

 

 

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*Trademarked by Ablynx

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